Cryptosporidium parvum-specific CD4 Th1 cells from sensitized donors responding to both fractionated and recombinant antigenic proteins

T-cell-mediated immunity plays a central role in the host response to Cryptosporidium parvum. Human T-cell clones (TCC) were isolated from peripheral blood mononuclear cells of five healthy donors with prior cryptosporidiosis by use of a C. parvum crude extract, two antigen fractions obtained by ion-exchange chromatography (IEC1 and IEC2), and two recombinant peptides (SA35 and SA40) from C. parvum sporozoites. The T-cell lines derived from the one recently infected donor had a higher proportion (26 to 38%) of T cells exhibiting the gamma/delta T-cell receptor (gamma/delta-TCR) than those from donors who had recovered from cryptosporidiosis several years earlier, suggesting that the gamma/delta T-cell population is involved in the early stage of the infection. The specific TCC had the alpha/beta-TCR, had the phenotype CD45RO(+) CD4(+) CD8(-), and were characterized by either hyperproduction of gamma interferon (IFN-gamma) alone, with a Th1 profile, or IFN-gamma hyperproduction together with interleukin-4 (IL-4) or IL-5 production, with a Th0 profile. SA35, SA40, IEC1, and IEC2 may be considered good targets of the cellular response against C. parvum and may play a role in maintaining the T-cell-mediated memory response to this parasite. Furthermore, the SA35 and SA40 peptides may be regarded as immunodominant antigens involved in the maintenance of the T-cell response in healthy C. parvum-sensitized persons.     

Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients

Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas, including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16.     

NGF-mediated sensitization of the excitability of rat sensory neurons is prevented by a blocking antibody to the p75 neurotrophin receptor

Nerve growth factor (NGF) can play a causal role in the initiation of hyperalgesia. Recent work demonstrates that NGF can act directly on nociceptive sensory neurons to augment their sensitivity to a variety of stimuli. Based on the existing literature, it is not clear whether this sensitization is mediated by the high-affinity TrkA receptor or the low-affinity p75 neurotrophin receptor. We examined whether a blocking antibody to the p75 neurotrophin receptor can prevent the NGF-induced enhancement of excitability in capsaicin-sensitive small-diameter sensory neurons that have been isolated from the adult rat. In this report, pretreatment with the p75 blocking antibody completely prevents the NGF-induced increase in the number of action potentials evoked by a ramp of depolarizing current as well as the suppression of a delayed rectifier-type of potassium current(s) in these neurons. Although the sensitization by NGF was blocked, the antibody had no effect on the capacity of ceramide, a putative downstream signaling molecule, to either enhance the excitability or inhibit the potassium current. These results indicate that NGF can increase the excitability of nociceptive sensory neurons through activation of the p75 neurotrophin receptor and its consequent liberation of ceramide from neuronal sphingomyelins.     

Interaction between pre-landing activities and stiffness regulation of the knee joint musculoskeletal system in the drop jump: implications to performance

The purpose of the present study was to investigate the interaction between the pre-landing activities and the stiffness regulation of the knee joint musculoskeletal system and the takeoff speed during a drop jump (DJ). Nine healthy male subjects performed a DJ test from the height of 50 cm. The surface electromyographic (EMG) activity of the vastus lateralis (VL) muscle was recorded to evaluate both the pre-landing and post-landing muscle activation levels. Simultaneous recording of the jumping motion and ground reaction force was performed by a high-speed video camera (100 frames·s^–1), and a force platform was employed to allow joint moment analysis. Joint stiffness was calculated by a linear regression of the knee joint moment/angle relationship. Elasticity of the knee extensor muscle during DJ was estimated by means of a four-element muscle model consisting of a parallel elastic component, a series elastic component (SEC), a viscous damper, and a contractile element. DJ performance correlated positively with the positive peak power of the knee joint (P<0.01) and with the moment of the knee joint at the end of stretch (P<0.01). However, there was no significant relationship between DJ performance and the positive peak power of the ankle joint. The knee joint moment at the end of stretch correlated with the SEC stiffness during the transmission phase from the end of the initial impact to the onset of the concentric action (P<0.01) and with the maximum rate of isometric force development of the knee extensors (P<0.01). Multiple regression analysis showed that the SEC stiffness during the transmission phase of the knee joint can be explained by a combination of the pre-activity of the VL muscle and the knee joint angular velocity at touchdown (F=5.76, P<0.05). These results seem to emphasize the functional significance of the pre-programmed activity for controlling the subsequent stiffness regulation and then contributing to the performance in DJ. Thus, it can be suggested that the centrally pre-programmed activity and the associated elastic behavior of the SEC in the knee extensor muscle in conjunction with the muscle contractile property play a major role in regulating the performance in DJ. Electronic Publication     

Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin

Background  

Using a rat model we have found that the bioflavonoid silymarin (SY) ameliorates some of the negative consequences of in utero exposure to ethanol (EtOH). In the current study our aim was to determine if laterality preference and corpus callosum development were altered in rat offspring whose mothers were provided with a concomitant administration of SY with EtOH throughout gestation.     

Active music therapy in Parkinson's disease: an integrative method for motor and emotional rehabilitation

BACKGROUND: Modern management of Parkinson's disease (PD) aims to obtain symptom control, to reduce clinical disability, and to improve quality of life. Music acts as a specific stimulus to obtain motor and emotional responses by combining movement and stimulation of different sensory pathways. We explored the efficacy of active music therapy (MT) on motor and emotional functions in patients with PD. METHODS: This prospective, randomized, controlled, single-blinded study lasted 3 months. It consisted of weekly sessions of MT and physical therapy (PT). Thirty-two patients with PD, all stable responders to levodopa and in Hoehn and Yahr stage 2 or 3, were randomly assigned to two groups of 16 patients each. We assessed severity of PD with the Unified Parkinson's Disease Rating Scale, emotional functions with the Happiness Measure, and quality of life using the Parkinson's Disease Quality of Life Questionnaire. MT sessions consisted of choral singing, voice exercise, rhythmic and free body movements, and active music involving collective invention. PT sessions included a series of passive stretching exercises, specific motor tasks, and strategies to improve balance and gait. RESULTS: MT had a significant overall effect on bradykinesia as measured by the Unified Parkinson's Disease Rating Scale (p < .034). Post-MT session findings were consistent with motor improvement, especially in bradykinesia items (p < .0001). Over time, changes on the Happiness Measure confirmed a beneficial effect of MT on emotional functions (p < .0001). Improvements in activities of daily living and in quality of life were also documented in the MT group (p < .0001). PT improved rigidity (p < .0001). CONCLUSIONS: MT is effective on motor, affective, and behavioral functions. We propose active MT as a new method for inclusion in PD rehabilitation programs.     

Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

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Determination of urinary orotic acid and uracil by capillary zone electrophoresis

We describe a simple method for measuring orotic acid and uracil concentration in urine by capillary zone electrophoresis in 20 mM Na-borate buffer, pH 9.2. The method was applied for studying a patient with HHH (hyperomithinemia, hyperammonemia and homocitrullinuria) syndrome. A high value of uracil excretion was found during periods of relatively low orotic acid excretion and normal ammonemia. The orotic acid level in urine was increased by increasing protein intake.